Strategies to improve PD-1/PD-L1 blockade therapies in bladder cancer and other cancers include: (i) identifying host factors including genetics, immune state, and molecular subtype that drive a relevant response, (ii) assessing biomarkers and combinations of biomarkers to predict response and to personalize therapy, (iii) developing better tools to monitor immune effects, and (iv) selecting combination drug approaches/regimens to address multiple “defects” in the immune response in addition to PD-1/PD-L1 blockade. The gene discussed is CD274; the disease is cancer.